Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

Abstract The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic, patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.     

Oral administration of an edible-mushroom-derived protein inhibits the development of food-allergic reactions in mice

BACKGROUND: Food allergy is a common disease without effective treatment. Since strict elimination of food allergens may be difficult, strategies for effective intervention are urgently needed. OBJECTIVE: The aim was to investigate the prophylactic use of orally administrated FIP-fve, an immunomodulatory protein isolated from the edible mushroom Flammulina velutipes, in a murine model of food allergy. METHODS: BALB/c mice were immunized twice intraperitoneally with ovalbumin (OVA), at an interval of 2 weeks. Before and during each period of immunization, FIP-fve (200 microg per mouse) or phosphate-buffered saline was given orally every other day with a total of five doses. Then OVA-specific antibodies and cytokine profiles were determined. Subsequently, the mice were orally challenged with OVA. Symptoms of anaphylaxis, levels of plasma histamine, and histology of intestines were examined. RESULTS: Mice receiving oral FIP-fve treatment during sensitization to OVA had an impaired OVA-specific IgE response with a Th1-predominant cytokine profile. These mice were protected from systemic anaphylaxis-like symptoms induced by subsequent oral challenge with OVA. CONCLUSION: Oral administration of FIP-fve has a Th1-skewing effect on the development of the allergen-specific immune response, and may serve the purpose of immunoprophylaxis for food allergy and other allergic diseases.     

100例SARS患者外周血T淋巴细胞亚群分析

目的 :探讨SARS患者外周血T淋巴细胞亚群变化。方法 :采用流式细胞仪检测10 0例SARS住院患者外周血T淋巴细胞亚群。结果 :与正常组比较 ,SARS组白细胞总数显著下降 ,淋巴细胞百分数和绝对数显著下降 ,粒细胞绝对数显著下降 ,CD3 、CD4 、CD8 细胞绝对数显著下降 ,CD4 细胞百分数 ,CD8 细胞百分数及CD4 /CD8 比值差异无统计学意义。比较SARS患者各病程CD3 、CD4 、CD8 ,于病程第一至第三周较第四周下降明显 (P <0 .0 5 ) ,病程第一至第三周之间差别无显著性 (P >0 .0 5 ) ;结论 :SARS患者外周血T淋巴细胞亚群的变化对阐明SARS的发病机制有一定意义。     

癫痫患者的红细胞免疫粘附功能的初步研究

本文用Ｃ（３ｂ）受体花环试验及ＩＣ花环试验分别测定了５０例正常人及５０例癫痫患者的红细胞Ｃ（３ｂ）受体花环率及ＩＣ花环率。结果提示癫痫患者Ｃ（３ｂ）受体花环率（８．４６±３．９８％）明显低于正常对照组（１３．９２±４．３２％）（Ｐ＜０．００１），ＩＣ花环率（５．２２±２．５９％）稍低于正常对照组（５．９０±１．６７％）（Ｐ＜０．０５）。表明癫痫患者的红细胞免疫粘附功能是低下的。文章还对影响正常人及癫痫患者红细胞免疫粘附功能的因素进行了讨论。     

Antagonism of novel inotropic agents at A1 adenosine receptors and m-cholinoceptors in human myocardium

Summary The effects of the new inotropic agents saterinone, sulmazole, UD-CG 212.C1 and milrinone at A₁ adenosine receptors and m-cholinoceptors were evaluated in human myocardium from patients with heart failure. At A₁ adenosine receptors, all compounds inhibited ³H-DPCPX-binding to ventricular membrane preparations at micromolar concentrations. As judged from the K_i-values, the rank order of potency was saterinone > sulmazole > UD-CG 212.C1 > milrinone. The new inotropic agents also displaced the binding of ³H-QNB at m-cholinoceptors. Except for saterinone, the concentration ranges of mean K_i-values were considerably higher at m-cholinoceptors than at A₁ adenosine receptors. The rank order of potency was saterinone > sulmazole > UD-CG 212.Cl > milrinone. Competition of the A₁ adenosine receptor agonist R-PIA to ³H-DPCPX-binding showed a biphasic curve with a shallow slope (Hill coefficient n_H = 0.63) and revealed two affinity states of the A₁ adenosine receptor. In the presence of guanine nucleotides [Gpp(NH)p], the competition curve showed one low affinity class of binding sites and was shifted to the right. In contrast, the competition curves of the new inotropic agents were characterized by a monophasic, steeper slope (mean Hill coefficient n_H = 0.98). Guanine nucleotides had no effect. Similar results were obtained with saterinone and carbachol at m-cholinoceptors. Competition with carbachol revealed three affinity states of the m-cholinoceptor, the superhigh affinity binding was reversed by Gpp(NH)p. Competition with saterinone revealed one class of binding sites which was not influenced by Gpp(NH)p. Accordingly, in isolated, electrically driven human atrial trabeculae, the negative inotropic effect of adenosine was antagonized concentration-dependently by saterinone, sulmazole and UD-CG 212.Cl. Similarly the negative inotropic effect of carbachol was antagonized concentration-dependently by saterinone. It is concluded that the new inotropic agents bind to A₁ adenosine receptors and that their interaction is of antagonist nature. This mechanism might contribute to their capacity to enhance force of contraction by stimulation of cAMP-formation in addition to phosphodiesterase inhibition. The effects of saterinone may be partially due to antagonism at m-cholinoceptors. This is presumably not the case with the other inotropic agents studied given their low affinity for this receptor.Send offprint requests to M. Böhm at the above addressSupported by the Deutsche Forschungsgemeinschaft     

Comparative effects of enoximone and theophylline on plasma catecholamines and haemodynamics in cardiosurgical patients

Summary The release of endogenous catecholamines in aorto-coronary bypass graft patients receiving either 0.5 mg/kg enoximone (n=10), 4.0 mg/kg theophylline (n=10) or saline solution (control,n=10) has been studied, as well as certain haemodynamic parameters. Adrenaline (A) and noradrenaline (NA) concentrations were not significantly changed by the administration of enoximone. Theophylline caused a small increase in NA (+ 40% in the 1st min) and a marked increase in A (approximately + 7000% in the 1st min), which still remained elevated at the end of the investigation period (+ 220% in the 30th min). The major haemodynamic effects of enoximone were a significant increase in cardiac index (CI; + 35%) and a decrease in pulmonary capillary wedge pressure (PCWP; −27%), pulmonary artery pressure (PAP; −21%), RVEDV and RVESV, while the heart rate (HR) remained almost unchanged. The dominant haemodynamic effects of theophylline were an increase in HR (+ 26%; arrhythmia in 3 patients), PAP (+ 22%), and RVEDV (+ 19%), while REVESV (+ 26%), MAP (−16%), CI (−14%), and RVEF (−15%) fell significantly. It is concluded that the haemodynamic actions of enoximone are not mediated by catecholamine release, whereas the adverse cardiovascular effects of theophylline might partly be explained by the significant increase in plasma adrenaline.     

马桑内酯所致癫痫发作大鼠红细胞免疫粘附功能的研究

作者用红细胞Ｃ＿３ｂ受体花环试验和红细胞免疫复合物花环试验对马桑内酯所致癫痫发作大鼠红细胞免疫粘附功能的变化进行了观察，结果表明，癫痫组动物红细胞Ｃ＿３ｂ受体花环率明显低于对照组，而红细胞免疫复合物花环率相差不显著．提示癫痫发作可导致大鼠红细胞免疫粘附功能降低，因此在癫痫治疗中注意调整和增强患者的红细胞免疫功能具有重要意义。     

How adverse drug reactions can play a role in innovative drug research

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.     

旁路活化补体降低PMN吞杀绿脓杆菌力的实验研究

为证明论题,本文做了3项实验:(1)人血PMN培养单层加上酵母多糖活化人血清(ZAHS)。PMN的超氧离子(O_2~-)、特殊颗粒(SG)与胞内杀菌力(ICBA)明显平行下降,于6 h最低,0.05 ml的作用最强。(2)经小鼠尾静脉注射0.5ml ZAHS/鼠,6 h后活杀。肺和血内PMN的上述指标均明显降低;肺内病变明显:急性间质炎,灶性水肿出血和萎陷,肺血屏障亚微结构损伤。(3)经抗人C_3、C_5血清(AHC_(3.5)S)体外中和的ZAHS,在体内外实验中均失去其有害作用。提示:ZAHS的有害作用与C_3、C_5碎片有关,在剂量适中且吞菌前作用时间较长的条件下方显极效。有害作用的可能机制:杀菌且能致炎的O_2~-与SG大多已于吞菌前排放在胞外,所以PMN的ICBA下降;累积于组织内的则损害PMN自身及其邻近的肺血屏障。这便于MOF与感染发生。